CDC Breaks Down Recent Study Linking Flu Vaccine, Miscarriage

No Cause-and-Effect Relationship Demonstrated, Says FP Expert

Although evidence indicates that influenza vaccination is safe during pregnancy, data are limited for women in their first trimester, prompting a recent study(www.sciencedirect.com) that examined the incidence of miscarriage in women who received the vaccine.

The study found that women vaccinated early in pregnancy with a flu vaccine containing the pandemic H1N1 (H1N1pdm09) component who had also received the H1N1pdm09 vaccine component the previous season had an increased risk for spontaneous abortion (SAB) within the 28 days after vaccination.

"At this time, the CDC and ACIP have not changed the recommendation for influenza vaccination of pregnant women," said the agency's fact sheet. "It is recommended that pregnant women get a flu vaccine during any trimester of their pregnancy because flu poses a danger to pregnant women, and a flu vaccine can prevent influenza in pregnant women."

Story highlights

Although evidence indicates that influenza vaccination is safe during pregnancy, data are limited for women in their first trimester, prompting a recent study that examined the incidence of miscarriage in women who received the vaccine.

The study found that women vaccinated early in pregnancy with a flu vaccine containing the pandemic H1N1 (H1N1pdm09) component who had also received the H1N1pdm09 vaccine component the previous season had an increased risk for spontaneous abortion within the 28 days after vaccination.

The CDC and its Advisory Committee on Immunization Practices continue to recommend that pregnant women get the flu vaccine at any point during their pregnancy because these women are at high risk for flu complications.

The CDC also recommended physicians talk with their pregnant patients about the flu vaccine and address any concerns they might have.

"Providers should use their clinical judgement based on various factors, including their patient's health status, local influenza activity, and the benefits versus the potential risks from flu vaccination when deciding whether and/or when to immunize their patient against influenza," the guidance said.

Study Details

Researchers analyzed data from the Vaccine Safety Datalink (VSD), a collaboration between the CDC's Immunizations Safety Office and several integrated health care organizations across the United States. The VSD uses electronic health information from more than 9 million patients, or about 3 percent of the U.S. population.

Information the researchers pulled from this system included demographic characteristics, vaccination records and medical outcomes. The study examined data from a small subgroup of women who received H1N1-containing vaccines in consecutive years.

Published online Sept. 13 in the journal Vaccine, the study compared 485 women ages 18-44 who miscarried to 485 women ages 18-44 who didn't miscarry to determine whether the women who had miscarriages were more or less likely to have received the 2010-2011 or 2011-2012 flu vaccine one to 28 days before their date of miscarriage.

In a season-specific analysis, the adjusted odds ratio (aOR) for vaccine receipt within the 28-day window was 3.7 in 2010-11 and 1.4 in 2011-12.

Among women who received pH1N1-containing vaccine during the previous influenza season, the aOR for vaccine receipt within the 28-day window was 7.7, whereas the aOR for the same period was 1.3 among women not vaccinated during the previous season.

Data showed that although several miscarriages occurred in the second trimester, most of them occurred during the first trimester; the median gestational age at the time of miscarriage was seven weeks.

According to the researchers, it's important to note that this was a case-control study that estimated an odds ratio of influenza vaccination among women who had a miscarriage compared with those who did not. The study did not estimate risk of miscarriage after flu vaccination, and therefore, the findings cannot be used to estimate the probability of miscarriage for pregnant women who received a pH1N1-containing flu vaccination in two consecutive years.

Among the study's limitations were small sample size and the possibility that vaccination records for these pregnant women could have been incomplete because the flu shots may have been administered in a setting other than their usual site of care. Furthermore, many miscarriages occur early in pregnancy and may not come to medical attention. Finally, it's not known how many women knew they were pregnant at the time of vaccination.

The CDC cited other studies that examined the effects of influenza vaccination on pregnant women and their infants, including a 2013 study(journals.lww.com) that also used VSD data and found no increased risk of pregnancy loss among pregnant women in the four weeks after receiving flu vaccine during the 2005-2006 and 2006-2007 flu seasons.

The agency noted there's an ongoing investigation to study this issue among women who were pregnant and eligible to receive flu vaccine during the 2012-2013 through 2014-2015 flu seasons, with results anticipated in late 2018 or 2019.

Keeping Things in Perspective

Recent AAFP Vaccine Science Fellow John Merrill-Steskal, M.D., of Ellensburg, Wash., told AAFP News that although a study like this may seem alarming, it's important to look at the big picture and remember how science works.

"The study raised a concern that is contrary to current medical perspective, a concern that needs to be considered further," he said. "This does not mean that because of this study, the flu vaccine should not be given in early pregnancy."

Merrill-Steskal reiterated that the study has significant limitations, including that because it was small, there's an increased possibility that the results may have occurred simply by chance.

"In addition, the study did not show a cause-and-effect relationship," he said. "A medical study may show a link or association between two things, but it is important to know if there is a true cause-and-effect relationship. Not uncommonly, with additional research, no cause-and-effect relationship is later found."

Finally, Merrill-Steskal said it's important to keep all of this in perspective.

"Most research supports the benefit of influenza vaccination throughout pregnancy," he said. "Influenza infection during pregnancy is often much more severe for the mother and can cause hospitalization or death. Meanwhile, influenza during pregnancy for the developing baby can cause birth defects and miscarriage."

Merrill-Steskal said he understands the concerns this study raises for expectant mothers who want the best for their child.

"While it will be important to have additional larger medical studies to follow up on the concern recently raised, the preponderance of medical research tells us that receiving influenza vaccine during early pregnancy is safe and is more likely to save both the mother's, as well as developing infant's, life," he said. "This is the message I think should be conveyed to patients."